Integrated surgical system and method for treatment in the irido-corneal angle of the eye

ABSTRACT

Intraocular pressure in an eye is reduced by delivering each of a high resolution optical coherence tomography (OCT) beam and a high resolution laser beam through the cornea, and the anterior chamber into the irido-corneal angle along an angled beam path. The OCT beam provides OCT imaging for diagnostic purposes and surgery planning and monitoring, while the laser beam is configured to modify tissue. A volume of ocular tissue within an outflow pathway in the irido-corneal angle is modified to reduce a pathway resistance present in one or more of the trabecular meshwork, the Schlemm&#39;s canal, and the one or more collector channels by applying the laser beam to ocular tissue defining the volume to thereby cause photo-disruptive interaction with the ocular tissue to reduce the pathway resistance or create a new outflow pathway.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a divisional application of U.S. patent applicationSer. No. 16/036,833, filed Jul. 16, 2018, for “Integrated SurgicalSystem and Method for Treatment in the Irido-Corneal Angle of the Eye,”the entire disclosure of which is incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates generally to the field of medical devicesand treatment of diseases in ophthalmology, and more particularly tosystems, apparatuses, and methods for treatment of tissues, especiallyocular tissue structures in the irido-corneal angle of the eye, for thelaser surgery treatment of glaucoma.

BACKGROUND

Before describing the different types of glaucoma and current diagnosisand treatments options, a brief overview of the anatomy of the eye isprovided.

Anatomy of the Eye

With reference to FIGS. 1-3, the outer tissue layer of the eye 1includes a sclera 2 that provides the structure of the eye's shape. Infront of the sclera 2 is a cornea 3 that is comprised of transparentlayers of tissue that allow light to enter the interior of the eye.Inside the eye 1 is a crystalline lens 4 that is connected to the eye byfiber zonules 5, which are connected to the ciliary body 6. Between thecrystalline lens 4 and the cornea 3 is an anterior chamber 7 thatcontains a flowing clear liquid called aqueous humor 8. Encircling theperimeter of the crystalline lens 4 is an iris 9 which forms a pupilaround the approximate center of the crystalline lens. A posteriorchamber 10 is located between the crystalline lens 4 and the retina 11.Light entering through the cornea 3 is optically focused through thecrystalline lens 4.

With reference to FIG. 2, the corneoscleral junction of the eye is theportion of the anterior chamber 7 at the intersection of the iris 9 andthe sclera 2. The anatomy of the eye 1 at the corneoscleral junctionincludes a trabecular meshwork 12. The trabecular meshwork 12 is afibrous network of tissue that encircles the iris 9 within the eye 1.The base of the trabecular meshwork 12 and the edge of the iris 9 areattached together at the scleral spur 14. The network of tissue layersthat make up the trabecular meshwork 12 are porous and thus present apathway for the egress of aqueous humor 8 flowing from the anteriorchamber 7. This pathway may be referred to herein as an aqueous humoroutflow pathway, an aqueous outflow pathway, or simply an outflowpathway

Referring to FIG. 3, the pathway formed by the pores in the trabecularmeshwork 12 connect to a set of thin porous tissue layers called theuveal 15, the corneoscleral meshwork 16, and the juxtacanalicular tissue17. The juxtacanalicular tissue 17, in turn, abuts a structure calledSchlemm's canal 18. The Schlemm's canal 18 carries a mixture of aqueoushumor 8 and blood from the surrounding tissue to drain into the venoussystem though a system of collector channels 19. As shown in FIG. 2, thevascular layer of the eye, referred to as the choroid 20, is next to thesclera 2. A space, called the suprachoroidal space 21, may be presentbetween the choroid 20 and the suprachoroidal space 21. The generalregion near the periphery of the wedge between the cornea 3 and the iris9, running circumferentially is called the irido-corneal angle 13. Theirido-corneal angle 13 may also be referred to as the corneal angle ofthe eye or simply the angle of the eye. The ocular tissues illustratedin FIG. 3 are all considered to be within the corneal angle 13.

With reference to FIG. 4, two possible outflow pathways for the movementof aqueous humor 8 include a trabecular outflow pathway 40 and auveoscleral outflow pathway 42. Aqueous humor 8, which is produced bythe ciliary body 6, flows from the posterior chamber 10 through thepupil into the anterior chamber 7, and then exits the eye through one ormore of the two different outflow pathways 40, 42. Approximately 90% ofthe aqueous humor 8 leaves via the trabecular outflow pathway 40 bypassing through the trabecular meshwork 12, into the Schlemm's canal 18and through one or more plexus of collector channels 19 before drainingthrough a drain path 41 into the venous system. Any remaining aqueoushumor 8 leaves primarily through the uveoscleral outflow pathway 42. Theuveoscleral outflow pathway 42 passes through the ciliary body 6 faceand iris root into the suprachoroidal space 21 (shown in FIG. 2).Aqueous humor 8 drains from the suprachoroidal space 21, from which itcan be drained through the sclera 2.

Aqueous humor 8 outflow through the trabecular outflow pathway 40 ispressure dependent in that outflow increase as the intraocular pressureincreases, whereas aqueous humor 8 outflow through the uveoscleraloutflow pathway 42 is pressure independent. Resistance to the outflow ofaqueous humor 8 through the trabecular outflow pathway 40 may lead toelevated intra-ocular pressure of the eye, which is a widely recognizedrisk factor for glaucoma. Resistance through the trabecular outflowpathway 40 may increase due a collapsed Schlemm's canal 18 or thepresence of a high density of collector channels 19.

Referring to FIG. 5, as an optical system, the eye 1 is represented byan optical model described by idealized centered and rotationallysymmetrical surfaces, entrance and exit pupils, and six cardinal points:object and image space focal points, first and second principal planes,and first and second nodal points. Angular directions relative to thehuman eye are often defined with respect to an optical axis 24, a visualaxis 26, a pupillary axis 28 and a line of sight 29 of the eye. Theoptical axis 24 is the symmetry axis, the line connecting the verticesof the idealized surfaces of the eye. The visual axis 26 connects thefoveal center 22 with the first and second nodal points to the object.The line of sight 29 connects the fovea through the exit and entrancepupils to the object. The pupillary axis 28 is normal to the anteriorsurface of the cornea 3 and directed to the center of the entrancepupil. These axes of the eye differ from one another only by a fewdegrees and fall within a range of what is generally referred to as thedirection of view.

Glaucoma

Glaucoma is a group of diseases that can harm the optic nerve and causevision loss or blindness. It is the leading cause of irreversibleblindness. Approximately 80 million people are estimated to haveglaucoma worldwide and of these, approximately 6.7 million arebilaterally blind. More than 2.7 million Americans over age 40 haveglaucoma. Symptoms start with loss of peripheral vision and can progressto blindness.

There are two forms of glaucoma, one is referred to as closed-angleglaucoma, the other as open-angled glaucoma. With reference to FIGS.1-4, in closed-angle glaucoma, the iris 9 in a collapsed anteriorchamber 7 may obstruct and close off the flow of aqueous humor 8. Inopen-angle glaucoma, which is the more common form of glaucoma, thepermeability of ocular tissue may be affected by blockage of tissue inthe irido-corneal angle 13 along the trabecular outflow pathway 40 or bythe collapse of the Schlemm's canal 18 or collector channels 19.

As previously stated, elevated intra-ocular pressure (IOP) of the eye,which damages the optic nerve, is a widely recognized risk factor forglaucoma. However, not every person with increased eye pressure willdevelop glaucoma, and glaucoma can develop without increased eyepressure. Nonetheless, it is desirable to reduce elevated IOP of the eyeto reduce the risk of glaucoma.

Methods of diagnosing conditions of the eye of a patient with glaucomainclude visual acuity tests and visual field tests, dilated eye exams,tonometry, i.e. measuring the intra-ocular pressure of the eye, andpachymetry, i.e. measuring the thickness of the cornea. Deterioration ofvision starts with the narrowing of the visual field and progresses tototal blindness. Imaging methods include slit lamp examination,observation of the irido-corneal angle with a gonioscopic lens andoptical coherence tomography (OCT) imaging of the anterior chamber andthe retina

Once diagnosed, some clinically proven treatments are available tocontrol or lower the intra-ocular pressure of the eye to slow or stopthe progress of glaucoma. The most common treatments include: 1)medications, such as eye drops or pills, 2) laser surgery, and 3)traditional surgery. Treatment usually begins with medication. However,the efficacy of medication is often hindered by patient non-compliance.When medication does not work for a patient, laser surgery is typicallythe next treatment to be tried. Traditional surgery is invasive, morehigh risk than medication and laser surgery, and has a limited timewindow of effectiveness. Traditional surgery is thus usually reserved asa last option for patients whose eye pressure cannot be controlled withmedication or laser surgery.

Laser Surgery

With reference to FIG. 2, laser surgery for glaucoma target thetrabecular meshwork 12 to decrease aqueous humor 8 flow resistance andincrease aqueous humor outflow. Common laser treatments include ArgonLaser Trabeculoplasty (ALT), Selective Laser Trabeculoplasty (SLT) andExcimer Laser Trabeculostomy (ELT).

ALT was the first laser trabeculoplasty procedure. During the procedure,an argon laser of 514 nm wavelength is applied to the trabecularmeshwork 12 around 180 degrees of the circumference of the irido-cornealangle 13. The argon laser induces a thermal interaction with the oculartissue that produces openings in the trabecular meshwork 12. ALT,however, causes scarring of the ocular tissue, followed by inflammatoryresponses and tissue healing that may ultimately close the openingthrough the trabecular meshwork 12 formed by the ALT treatment, thusreducing the efficacy of the treatment. Furthermore, because of thisscarring, ALT therapy is typically not repeatable.

SLT is designed to lower the scarring effect by selectively targetingpigments in the trabecular meshwork 12 and reducing the amount of heatdelivered to surrounding ocular tissue. During the procedure, a solidstate laser of 532 nm wavelength is applied to the trabecular meshwork12 between 180 to 360 degrees around the circumference of theirido-corneal angle 13 to produce openings through the trabecularmeshwork 12. SLT treatment can be repeated, but subsequent treatmentshave lower effects on IOP reduction.

ELT uses a 308 nm wavelength ultraviolet (UV) excimer laser andnon-thermal interaction with ocular tissue to treat the trabecularmeshwork 12 in a manner that does not invoke a healing response.Therefore, the IOP lowering effect lasts longer. However, because the UVlight of the laser cannot penetrate deep into the eye, the laser lightis delivered to the trabecular meshwork 12 via an optical fiber insertedinto the eye 1 through an opening and the fiber is brought into contactwith the trabecular meshwork. The procedure is highly invasive and isgenerally practiced simultaneously with cataract procedures when the eyeis already surgically open. Like ALT and SLT, ELT also lacks controlover the amount of IOP reduction.

None of these existing laser treatments represents an ideal treatmentfor glaucoma. Accordingly, what is needed are systems, apparatuses, andmethod for laser surgery treatment of glaucoma that effectively reduceIOP without significant scarring of tissue, so the treatment may becompleted in a single procedure and repeated at a later time ifnecessary.

SUMMARY

The present disclosure relates to a method of reducing intraocularpressure in an eye having a cornea, an anterior chamber, and anirido-corneal angle comprising an aqueous humor outflow pathway formedof a trabecular meshwork, a Schlemm's canal, and one or more collectorchannels branching from the Schlemm's canal. The method includesdelivering each of an optical coherence tomography (OCT) beam and alaser beam through the cornea, and the anterior chamber into theirido-corneal angle. The method further includes modifying a volume ofocular tissue within the outflow pathway to reduce a pathway resistancepresent in one or more of the trabecular meshwork, the Schlemm's canal,and the one or more collector channels by applying the laser beam toocular tissue defining the volume to thereby cause photo-disruptiveinteraction with the ocular tissue to reduce the pathway resistance orcreate a new outflow pathway.

In an aspect of this method, each of an OCT beam and a laser beam aredelivered to the irido-corneal angle by directing each beam to a firstoptical subsystem that includes a window coupled to the cornea and anexit lens coupled to the window. The eye, by nature, comprises adirection of view and the first optical subsystem is characterized by afirst optical axis that is substantially aligned with the direction ofview when the first optical system is coupled to the eye. Distortion andrefraction of the beams along the way to the irido-corneal angle arecompensated for by directing each beam into the first optical subsystemalong a second optical axis offset from the first optical axis by anangle α. The exit lens comprises a convex surface and distortion andrefraction is further compensated for by directing each beam into theconvex surface of the exit lens at an angle β relative to a surfacenormal to the convex surface.

In further aspects of the method, the OCT beam and the laser beam may becollinearly directed or non-collinearly directed to the first opticalsubsystem. The OCT beam is configured to provide high resolution images,while the laser beam is configured to provide high precision tissuemodification. To this end, each beam may have substantially equalresolutions, on the order of approximately 5 micrometers. The laser beamis configured to initiate disruptive interaction with the ocular tissueto creates a channel opened through the trabecular meshwork connectingthe anterior chamber and the Schlemm's canal. To this end, the laserbeam may have a wavelength between 330 nanometers and 2000 nanometersand may be delivered as a multitude of laser pulses with pulse durationbetween 20 femtoseconds and 1 nanosecond.

The present disclosure also relates to an integrated surgical system forreducing intraocular pressure in an eye having a cornea, an anteriorchamber, and an irido-corneal angle comprising an aqueous humor outflowpathway formed of a trabecular meshwork, a Schlemm's canal, and one ormore collector channels branching from the Schlemm's canal. The systemincludes a first optical subsystem, a second a first optical subsystem,and a control system. The a first optical subsystem includes a windowconfigured to be coupled to the cornea, and an exit lens configured tobe coupled to the window. The second optical subsystem includes an OCTimaging apparatus configured to output an OCT beam, a laser sourceconfigured to output a laser beam, and a plurality of componentsconfigured to one or more of condition, scan, combine, and direct one ormore of the OCT beam and the laser beam.

The control system is coupled to the second optical subsystem and isconfigured to instruct the OCT imaging apparatus to output an OCT beamand the laser source to output a laser beam, for delivery through thecornea, and the anterior chamber into the irido-corneal angle. Thecontrol system is also configured to instruct the laser source to modifya volume of ocular tissue within the outflow pathway to reduce a pathwayresistance present in one or more of the trabecular meshwork, theSchlemm's canal, and the one or more collector channels by applying thelaser beam to ocular tissue defining the volume to thereby causephoto-disruptive interaction with the ocular tissue to reduce thepathway resistance or create a new outflow pathway.

In one aspect of the system, the second optical subsystem is configuredto direct the OCT beam and the laser beam toward the first opticalsubsystem. In a further aspect, the eye is characterized by a directionof view, the first optical subsystem by a first optical axis, and thefirst optical subsystem is adapted to be coupled to the eye so that thefirst optical axis is substantially aligned with the direction of view.The OCT beam and the laser beam are directed toward the first opticalsubsystem along a second optical axis offset from the first optical axisby an angle α. In an additional aspect, the exit lens has a convexsurface and the OCT beam and the laser beam are directed into the convexsurface of the exit lens at an angle β relative to a surface normal tothe convex surface.

In further aspects, the control system is further configured to instructthe OCT imaging apparatus to acquire a diagnostic OCT image of a portionof the irido-corneal angle prior to ocular tissue modification. Based onthis image, the control system determines the volume of ocular tissue tomodify based on the OCT image. In a detailed aspect, the control systemis configured to determine the volume of ocular tissue to modify bydetermining a density distribution of collector channels around at leasta portion of the circumference of the Schlemm's canal, identifying aregion of the Schlemm's canal having a density above a thresholdcriterion; and including the proximity of the identified region in thevolume of ocular tissue to modify.

It is understood that other aspects of apparatuses and methods willbecome apparent to those skilled in the art from the following detaileddescription, wherein various aspects of apparatuses and methods areshown and described by way of illustration. As will be realized, theseaspects may be implemented in other and different forms and its severaldetails are capable of modification in various other respects.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not as restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of systems, apparatuses, and methods will now bepresented in the detailed description by way of example, and not by wayof limitation, with reference to the accompanying drawings, wherein:

FIG. 1 is a sectional schematic illustration of a human eye and itsinterior anatomical structures.

FIG. 2 is a sectional schematic illustration of the irido-corneal angleof the eye of FIG. 1.

FIG. 3 is a sectional schematic illustration detailing anatomicalstructures in the irido-corneal angle of FIG. 2, including thetrabecular meshwork, Schlemm's canal, and one or more collector channelsbranching from the Schlemm's canal.

FIG. 4 is a sectional schematic illustration of various outflow pathwaysfor aqueous humor through the trabecular meshwork, Schlemm's canal, andcollector channels of FIG. 3.

FIG. 5 is a sectional schematic illustration of a human eye showingvarious axes associated with the eye.

FIG. 6 is a sectional schematic illustration of an angled beam pathalong which one or more light beams may access the irido-corneal angleof the eye.

FIG. 7 is a block diagram of an integrated surgical system fornon-invasive glaucoma surgery including a control system, a femtosecondlaser source, an OCT imaging apparatus, a microscope, beam conditionersand scanners, beam combiners, a focusing objective, and a patientinterface.

FIG. 8 is a detailed block diagram of the integrated surgical system ofFIG. 7.

FIGS. 9a and 9b are schematic illustrations of the focusing objective ofthe integrated surgical system of FIG. 7 coupled to (FIG. 9a ) anddecoupled from (FIG. 9b ) the patient interface of the integratedsurgical system of FIG. 7.

FIG. 9c is a schematic illustration of components of the focusingobjective and the patient interface included in FIGS. 9a and 9 b.

FIGS. 10a and 10b are schematic illustrations of components of theintegrated surgical system of FIGS. 7 and 8 functionally arranged toform a first optical system and a second optical subsystem that enableaccess to the to the irido-corneal angle along the angled beam path ofFIG. 6.

FIG. 10c is a schematic illustration of a beam passing through the firstoptical subsystem of FIGS. 10a and 10b and into the eye.

FIGS. 11a and 11b are schematic illustrations of a surgical volume (FIG.11a ) determined by the integrated surgical system of FIG. 7. and anoutflow pathway (FIG. 11b ) formed at the surgical volume by theintegrated surgical system.

FIG. 12 is a flowchart of a method of modifying ocular tissue at theirido-corneal angle of the eye.

FIG. 13 is a flowchart of a method of delivering light beams to theirido-corneal angle of the eye along the angled beam path of FIG. 6.

DETAILED DESCRIPTION

Disclosed herein are systems, apparatuses, and methods for safely andeffectively reducing intra-ocular pressure (IOP) in the eye to eithertreat or reduce the risk of glaucoma. The systems, apparatuses, andmethods enable access to the irido-corneal angle of the eye andintegrate laser surgery techniques with high resolution imaging toprecisely diagnose, locate, and treat abnormal ocular tissue conditionswithin the irido-corneal angle that may be causing elevated IOP.

An integrated surgical system disclosed herein is configured to reduceintraocular pressure in an eye having a cornea, an anterior chamber, andan irido-corneal angle comprising an aqueous humor outflow pathwayformed of a trabecular meshwork, a Schlemm's canal, and one or morecollector channels branching from the Schlemm's canal. The integratedsurgical system also includes a first optical subsystem and a secondoptical subsystem. The first optical subsystem includes a windowconfigured to be coupled to the cornea and an exit lens configured to becoupled to the window. The second optical subsystem includes an opticalcoherence tomography (OCT) imaging apparatus configured to output an OCTbeam, a laser source configured to output a laser beam, and a pluralityof components, e.g., lenses and mirrors, configured to condition,combine, or direct the OCT beam and the laser beam toward the firstoptical subsystem.

The integrated surgical system also includes a control system coupled tothe OCT imaging apparatus, the laser source, and the second opticalsubsystem. The controller is configured to instruct the OCT imagingapparatus to output an OCT beam and the laser source to output a laserbeam, for delivery through the cornea, and the anterior chamber into theirido-corneal angle. In one configuration, the control system controlsthe second optical subsystem, so the OCT beam and the laser beam aredirected into the first optical subsystem along a second optical axisthat is offset from the first optical axis and that extends into theirido-corneal angle along an angled beam path 30.

Directing each of an OCT beam and a laser beam along the same secondoptical axis into the irido-corneal angle of the eye is beneficial inthat it enables direct application of the result of the evaluation ofthe condition into the treatment plan and surgery with precision in oneclinical setting. Furthermore, combining OCT imaging and laser treatmentallows targeting the ocular tissue with precision not available with anyexisting surgical systems and methods. Surgical precision afforded bythe integrated surgical system allows for the affecting of only thetargeted tissue of microscopic size and leaves the surrounding tissueintact. The microscopic size scale of the affected ocular tissue to betreated in the irido-corneal angle of the eye ranges from a fewmicrometers to a few hundred micrometers. For example, with reference toFIGS. 2 and 3, the cross-sectional size of the normal Schlemm's canal 18is an oval shape of a few tens of micrometers by a few hundredmicrometers. The diameter of collector channels 19 and veins is a fewtens of micrometers. The thickness of the juxtacanalicular tissue 17 isa few micrometers, the thickness of the trabecular meshwork 12 is arounda hundred micrometers.

The control system of the integrated surgical system is furtherconfigured to instruct the laser source to modify a volume of oculartissue within the outflow pathway to reduce a pathway resistance presentin one or more of the trabecular meshwork, the Schlemm's canal, and theone or more collector channels by applying the laser beam to oculartissue defining the volume to thereby cause photo-disruptive interactionwith the ocular tissue to reduce the pathway resistance or create a newoutflow pathway.

The laser source may be a femtosecond laser. Femtosecond lasers providenon-thermal photo-disruption interaction with ocular tissue to avoidthermal damage to surrounding tissue. Further, unlike other surgicalmethods, with femtosecond laser treatment opening surface incisionspenetrating the eye can be avoided, enabling a non-invasive treatment.Instead of performing the treatment in a sterile surgical room, thenon-invasive treatment can be performed in a non-sterile outpatientfacility.

An additional imaging component may be included the integrated surgicalsystem to provide direct visual observation of the irido-corneal anglealong an angle of visual observation. For example, a microscope orimaging camera may be included to assist the surgeon in the process ofdocking the eye to the patient interface or an immobilizing device,location of ocular tissues in the eye and observing the progress of thesurgery. The angle of visual observation can also be along the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7.

Images from the OCT imaging apparatus and the additional imagingcomponent providing visual observation, e.g. microscope, are combined ona display device such as a computer monitor. Different images can beregistered and overlaid on a single window, enhanced, processed,differentiated by false color for easier understanding. Certain featuresare computationally recognized by a computer processor, imagerecognition and segmentation algorithm can be enhanced, highlighted,marked for display. The geometry of the treatment plan can also becombined and registered with imaging information on the display deviceand marked up with geometrical, numerical and textual information. Thesame display can also be used for user input of numerical, textual andgeometrical nature for selecting, highlighting and marking features,inputting location information for surgical targeting by keyboard,mouse, cursor, touchscreen, audio or other user interface devices.

OCT Imaging

The main imaging component of the integrated surgical system disclosedherein is an OCT imaging apparatus. OCT technology may be used todiagnose, locate and guide laser surgery directed to the irido-cornealangle of the eye. For example, with reference to FIGS. 1-3, OCT imagingmay be used to determine the structural and geometrical conditions ofthe anterior chamber 7, to assess possible obstruction of the trabecularoutflow pathway 40 and to determine the accessibility of the oculartissue for treatment. As previously described, the iris 9 in a collapsedanterior chamber 7 may obstruct and close off the flow of aqueous humor8, resulting in closed-angle glaucoma. In open-angle glaucoma, where themacroscopic geometry of the angle is normal, the permeability of oculartissue may be affected, by blockage of tissue along the trabecularoutflow pathway 40 or by the collapse of the Schlemm's canal 18 orcollector channels 19.

OCT imaging can provide the necessary spatial resolution, tissuepenetration and contrast to resolve microscopic details of oculartissue. When scanned, OCT imaging can provide two-dimensional (2D)cross-sectional images of the ocular tissue. As another aspect of theintegrated surgical system, 2D cross-sectional images may be processedand analyzed to determine the size, shape and location of structures inthe eye for surgical targeting. It is also possible to reconstructthree-dimensional (3D) images from a multitude of 2D cross-sectionalimages but often it is not necessary. Acquiring, analyzing anddisplaying 2D images is faster and can still provide all informationnecessary for precise surgical targeting.

OCT is an imaging modality capable of providing high resolution imagesof materials and tissue. Imaging is based on reconstructing spatialinformation of the sample from spectral information of scattered lightfrom within the sample. Spectral information is extracted by using aninterferometric method to compare the spectrum of light entering thesample with the spectrum of light scattered from the sample. Spectralinformation along the direction that light is propagating within thesample is then converted to spatial information along the same axis viathe Fourier transform. Information lateral to the OCT beam propagationis usually collected by scanning the beam laterally and repeated axialprobing during the scan. 2D and 3D images of the samples can be acquiredthis way. Image acquisition is faster when the interferometer is notmechanically scanned in a time domain OCT, but interference from a broadspectrum of light is recorded simultaneously, this implementation iscalled a spectral domain OCT. Faster image acquisition may also beobtained by scanning the wavelength of light rapidly from a wavelengthscanning laser in an arrangement called a swept-source OCT.

The axial spatial resolution limit of the OCT is inversely proportionalto the bandwidth of the probing light used. Both spectral domain andswept source OCTs are capable of axial spatial resolution below 5micrometers (μm) with sufficiently broad bandwidth of 100 nanometers(nm) or more. In the spectral domain OCT, the spectral interferencepattern is recorded simultaneously on a multichannel detector, such as acharge coupled device (CCD) or complementary metal oxide semiconductor(CMOS) camera, while in the swept source OCT the interference pattern isrecorded in sequential time steps with a fast optical detector andelectronic digitizer. There is some acquisition speed advantage of theswept source OCT but both types of systems are evolving and improvingrapidly, and resolution and speed is sufficient for purposes of theintegrated surgical system disclosed herein. Stand-alone OCT systems andOEM components are now commercially available from multiple vendors,such as Optovue Inc., Fremont, Calif., Topcon Medical Systems, Oakland,N.J., Carl Zeiss Meditec AG, Germany, Nidek, Aichi, Japan, Thorlabs,Newton, N.J., Santec, Aichi, Japan, Axsun, Billercia, Mass., and othervendors.

Femtosecond Laser Source

The preferred surgical component of the integrated surgical systemdisclosed herein is a femtosecond laser. A femtosecond laser provideshighly localized, non-thermal photo-disruptive laser-tissue interactionwith minimal collateral damage to surrounding ocular tissue.Photo-disruptive interaction of the laser is utilized in opticallytransparent tissue. The principal mechanism of laser energy depositioninto the ocular tissue is not by absorption but by a highly nonlinearmultiphoton process. This process is effective only at the focus of thepulsed laser where the peak intensity is high. Regions where the beam istraversed but not at the focus are not affected by the laser. Therefore,the interaction region with the ocular tissue is highly localized bothtransversally and axially along the laser beam. The process can also beused in weakly absorbing or weakly scattering tissue. While femtosecondlasers with photo-disruptive interactions have been successfully used inophthalmic surgical systems and commercialized in other ophthalmic laserprocedures, none have been used in an integrated surgical system thataccesses the irido-corneal angle.

In known refractive procedures, femtosecond lasers are used to createcorneal flaps, pockets, tunnels, arcuate incisions, lenticule shapedincisions, partial or fully penetrating corneal incisions forkeratoplasty. For cataract procedures the laser creates a circular cuton the capsular bag of the eye for capsulotomy and incisions of variouspatterns in the lens for braking up the interior of the crystalline lensto smaller fragments to facilitate extraction. Entry incisions throughthe cornea opens the eye for access with manual surgical devices and forinsertions of phaco emulsification devices and intra-ocular lensinsertion devices. Several companies have commercialized such surgicalsystems, among them the Intralase system now available from Jonhson &Johnson Vision, Santa Ana, Calif., The LenSx and Wavelight systems fromAlcon, Fort Worth, Tex., other surgical systems from Bausch and Lomb,Rochester, N.Y., Carl Zeiss Meditec AG, Germany, Ziemer, Port,Switzerland, and LensAR, Orlando, Fla.

These existing systems are developed for their specific applications,for surgery in the cornea, and the crystalline lens and its capsular bagand are not capable of performing surgery in the irido-corneal angle 13for several reasons. First, the irido-corneal angle 13 is not accessiblewith these surgical laser systems because the irido-corneal angle is toofar out in the periphery and is outside of surgical range of thesesystems. Second, the angle of the laser beam from these systems, whichis along the optical axis to the eye 24, is not appropriate to reachingthe irido-corneal angle 13, where there is significant scattering andoptical distortion at the applied wavelength. Third, any imagingcapabilities these systems may have do not have the accessibility,penetration depth and resolution to image the tissue along thetrabecular outflow pathway 40 with sufficient detail and contrast.

In accordance with the integrated surgical system disclosed herein,clear access to the irido-corneal angle 13 is provided along the angledbeam path 30. The tissue, e.g., cornea 3 and the aqueous humor 8 in theanterior chamber 7, along this angled beam path 30 is transparent forwavelengths from approximately 400 nm to 2500 nm and femtosecond lasersoperating in this region can be used. Such mode locked lasers work attheir fundamental wavelength with Titanium, Neodymium or Ytterbiumactive material. Non-linear frequency conversion techniques known in theart, frequency doubling, tripling, sum and difference frequency mixingtechniques, optical parametric conversion can convert the fundamentalwavelength of these lasers to practically any wavelength in the abovementioned transparent wavelength range of the cornea.

Existing ophthalmic surgical systems apply lasers with pulse durationslonger than 1 ns have higher photo-disruption threshold energy, requirehigher pulse energy and the dimension of the photo-disruptiveinteraction region is larger, resulting in loss of precision of thesurgical treatment. When treating the irido-corneal angle 13, however,higher surgical precision is required. To this end, the integratedsurgical system may be configured to apply lasers with pulse durationsfrom 10 femtosecond (fs) to 1 nanosecond (ns) for generatingphoto-disruptive interaction of the laser beam with ocular tissue in theirido-corneal angle 13. While lasers with pulse durations shorter than10 fs are available, such laser sources are more complex and moreexpensive. Lasers with the described desirable characteristics, e.g.,pulse durations from 10 femtosecond (fs) to 1 nanosecond (ns), arecommercially available from multiple vendors, such as Newport, Irvine,Calif., Coherent, Santa Clara, Calif., Amplitude Systems, Pessac,France, NKT Photonics, Birkerod, Denmark, and other vendors.

Accessing the Irido-Corneal Angle

An important feature afforded by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13. Withreference to FIG. 6, the irido-corneal angle 13 of the eye may beaccessed via the integrated surgical system along an angled beam path 30passing through the cornea 3 and through the aqueous humor 8 in theanterior chamber 7. For example, one or more of an imaging beam, e.g.,an OCT beam and/or a visual observation beam, and a laser beam mayaccess the irido-corneal angle 13 of the eye along the angled beam path30.

An optical system disclosed herein is configured to direct a light beamto an irido-corneal angle 13 of an eye along an angled beam path 30. Theoptical system includes a first optical subsystem and a second opticalsubsystem. The first optical subsystem includes a window formed of amaterial with a refractive index n_(w) and has opposed concave andconvex surfaces. The first optical subsystem also includes an exit lensformed of a material having a refractive index n_(x). The exit lens alsohas opposed concave and convex surfaces. The concave surface of the exitlens is configured to couple to the convex surface of the window todefine a first optical axis extending through the window and the exitlens. The concave surface of the window is configured to detachablycouple to a cornea of the eye with a refractive index n_(c) such that,when coupled to the eye, the first optical axis is generally alignedwith the direction of view of the eye.

The second optical subsystem is configured to output a light beam, e.g.,an OCT beam or a laser beam. The optical system is configured so thatthe light beam is directed to be incident at the convex surface of theexit lens along a second optical axis at an angle aα that is offset fromthe first optical axis. The respective geometries and respectiverefractive indices n_(x), and n_(w) of the exit lens and window areconfigured to compensate for refraction and distortion of the light beamby bending the light beam so that it is directed through the cornea 3 ofthe eye toward the irido-corneal angle 13. More specifically, the firstoptical system bends the light beam to that the light beam exits thefirst optical subsystem and enters the cornea 3 at an appropriate angleso that the light beam progresses through the cornea and the aqueoushumor 8 in a direction along the angled beam path 30 toward theirido-corneal angle 13.

Accessing the irido-corneal angle 13 along the angled beam path 30provides several advantages. An advantage of this angled beam path 30 tothe irido-corneal angle 13 is that the OCT beam and laser beam passesthrough mostly clear tissue, e.g., the cornea 3 and the aqueous humor 8in the anterior chamber 7. Thus, scattering of these beams by tissue isnot significant. With respect to OCT imaging, this enables the use ofshorter wavelength, less than approximately 1 micrometer, for the OCT toachieve higher spatial resolution. An additional advantage of the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7 is the avoidance of direct laser beam or OCT beamlight illuminating the retina 11. As a result, higher average powerlaser light and OCT light can be used for imaging and surgery, resultingin faster procedures and less tissue movement during the procedure.

Another important feature provided by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13 in away that reduces beam discontinuity. To this end, the window and exitlens components of the first optical subsystem are configured to reducethe discontinuity of the optical refractive index between the cornea 3and the neighboring material and facilitate entering light through thecornea at a steep angle.

Having thus generally described the integrated surgical system and someof its features and advantages, a more detailed description of thesystem and its component parts follows.

Integrated Surgical System

With reference to FIG. 7, an integrated surgical system 1000 fornon-invasive glaucoma surgery includes a control system 100, a surgicalcomponent 200, a first imaging component 300 and an optional secondimaging component 400. In the embodiment of FIG. 7, the surgicalcomponent 200 is a femtosecond laser source, the first imaging component300 is an OCT imaging apparatus, and the optional second imagingcomponent 400 is a visual observation apparatus, e.g., a microscope, fordirect viewing or viewing with a camera. Other components of theintegrated surgical system 1000 include beam conditioners and scanners500, beam combiners 600, a focusing objective 700, and a patientinterface 800.

The control system 100 may be a single computer or and plurality ofinterconnected computers configured to control the hardware and softwarecomponents of the other components of the integrated surgical system1000. A user interface 110 of the control system 100 acceptsinstructions from a user and displays information for observation by theuser. Input information and commands from the user include but are notlimited to system commands, motion controls for docking the patients eyeto the system, selection of pre-programmed or live generated surgicalplans, navigating through menu choices, setting of surgical parameters,responses to system messages, determining and acceptance of surgicalplans and commands to execute the surgical plan. Outputs from the systemtowards the user includes but are not limited to display of systemparameters and messages, display of images of the eye, graphical,numerical and textual display of the surgical plan and the progress ofthe surgery.

The control system 100 is connected to the other components 200, 300,400, 500 of the integrated surgical system 1000. Control signals fromthe control system 100 to the femtosecond laser source 200 function tocontrol internal and external operation parameters of the laser source,including for example, power, repetition rate and beam shutter. Controlsignals from the control system 100 to the OCT imaging apparatus 300function to control OCT beam scanning parameters, and the acquiring,analyzing and displaying of OCT images.

Laser beams 201 from the femtosecond laser source 200 and OCT beams 301from the OCT imaging apparatus 300 are directed towards a unit of beamconditioners and scanners 500. Different kind of scanners can be usedfor the purpose of scanning the laser beam 201 and the OCT beam 301. Forscanning transversal to a beam 201, 301, angular scanning galvanometerscanners are available for example from Cambridge Technology, Bedford,Mass., Scanlab, Munich, Germany. To optimize scanning speed, the scannermirrors are typically sized to the smallest size, which still supportthe required scanning angles and numerical apertures of the beams at thetarget locations. The ideal beam size at the scanners is typicallydifferent from the beam size of the laser beam 201 or the OCT beam 301,and different from what is needed at the entrance of a focusingobjective 700. Therefore, beam conditioners are applied before, after orin between individual scanners. The beam conditioner and scanners 500includes scanners for scanning the beam transversally and axially. Axialscanning changes the depth of the focus at the target region. Axialscanning can be performed by moving a lens axially in the beam path witha servo or stepper motor.

The laser beam 201 and the OCT beam 301 are combined with dichroic,polarization or other kind of beam combiners 600 to reach a commontarget volume or surgical volume in the eye. In an integrated surgicalsystem 1000 having a femtosecond laser source 200, an OCT imagingapparatus 300, and a visual observation device 400, the individual beams201, 301, 401 for each of these components may be individually optimizedand may be collinear or non-collinear to one another. The beam combiner600 uses dichroic or polarization beam splitters to split and recombinelight with different wavelength and/or polarization. The beam combiner600 may also include optics to change certain parameters of theindividual beams 201, 301, 401 such as beam size, beam angle anddivergence. Integrated visual illumination, observation or imagingdevices assist the surgeon in docking the eye to the system andidentifying surgical locations.

To resolve ocular tissue structures of the eye in sufficient detail, theimaging components 300, 400 of the integrated surgical system 1000 mayprovide an OCT beam and a visual observation beam having a spatialresolution of several micrometers. The resolution of the OCT beam is thespatial dimension of the smallest feature that can be recognized in theOCT image. It is determined mostly by the wavelength and the spectralbandwidth of the OCT source, the quality of the optics delivering theOCT beam to the target location in the eye, the numerical aperture ofthe OCT beam and the spatial resolution of the OCT imaging apparatus atthe target location. In one embodiment, the OCT beam of the integratedsurgical system has a resolution of no more than 5 μm.

Likewise, the surgical laser beam provided by the femtosecond lasersource 200 may be delivered to targeted locations with severalmicrometer accuracy. The resolution of the laser beam is the spatialdimension of the smallest feature at the target location that can bemodified by the laser beam without significantly affecting surroundingocular tissue. It is determined mostly by the wavelength of the laserbeam, the quality of the optics delivering the laser beam to targetlocation in the eye, the numerical aperture of the laser beam, theenergy of the laser pulses in the laser beam and the spatial resolutionof the laser scanning system at the target location. In addition, tominimize the threshold energy of the laser for photo-disruptiveinteraction, the size of the laser spot should be no more thanapproximately 5 μm.

It should be noted that, while the visual observation beam 401 isacquired by the visual observation device 400 using fixed, non-scanningoptics, the OCT beam 301 of the OCT imaging apparatus 300 is scannedlaterally in two transversal directions. The laser beam 201 of thefemtosecond laser source 200 is scanned in two lateral dimensions andthe depth of the focus is scanned axially.

For practical embodiments, beam conditioning, scanning and combining theoptical paths are certain functions performed on the laser, OCT andvisual observation optical beams. Implementation of those functions mayhappen in a different order than what is indicated in FIG. 7. Specificoptical hardware that manipulates the beams to implement those functionscan have multiple arrangements with regards to how the optical hardwareis arranged. They can be arranged in a way that they manipulateindividual optical beams separately, in another embodiment one componentmay combine functions and manipulates different beams. For example, asingle set of scanners can scan both the laser beam 201 and the OCT beam301. In this case, separate beam conditioners set the beam parametersfor the laser beam 201 and the OCT beam 301, then a beam combinercombines the two beams for a single set of scanners to scan the beams.While many combinations of optical hardware arrangements are possiblefor the integrated surgical system, the following section describes indetail an example arrangement.

Beam Delivery

In the following description, the term beam may—depending on thecontext—refer to one of a laser beam, an OCT beam, or a visualobservation beam. A combined beam refers to two or more of a laser beam,an OCT beam, or a visual observation beam that are either collinearlycombined or non-collinearly combined. Example combined beams include acombined OCT/laser beam, which is a collinear or non-colinearcombination of an OCT beam and a laser beam, and a combinedOCT/laser/visual beam, which is a collinear or non-collinear combinationof an OCT beam, a laser beam, and a visual beam. In a collinearlycombined beam, the different beams may be combined by dichroic orpolarization beam splitters, and delivered along a same optical paththrough a multiplexed delivery of the different beams. In anon-collinear combined beam, the different beams are delivered at thesame time along different optical paths that are separated spatially orby an angle between them. In the description to follow, any of theforegoing beams or combined beams may be generically referred to as alight beam. The terms distal and proximal may be used to designate thedirection of travel of a beam, or the physical location of componentsrelative to each other within the integrated surgical system. The distaldirection refers to a direction toward the eye; thus an OCT beam outputby the OCT imaging apparatus moves in the distal direction toward theeye. The proximal direction refers to a direction away from the eye;thus an OCT return beam from the eye moves in the proximal directiontoward the OCT imaging apparatus.

Referring to FIG. 8, an example integrated surgical system is configuredto deliver each of a laser beam 201 and an OCT beam 301 in the distaldirection toward an eye 1, and receive each of an OCT return beam andthe visual observation beam 401 back from the eye 1. Regarding thedelivery of a laser beam, a laser beam 201 output by the femtosecondlaser source 200 passes through a beam conditioner 510 where the basicbeam parameters, beam size, divergence are set. The beam conditioner 510may also include additional functions, setting the beam power or pulseenergy and shutter the beam to turn it on or off. After existing thebeam conditioner 510, the laser beam 210 enters an axial scanning lens520. The axial scanning lens 520, which may include a single lens or agroup of lenses, is movable in the axial direction 522 by a servo motor,stepper motor or other control mechanism. Movement of the axial scanninglens 520 in the axial direction 522 changes the axial distance of thefocus of the laser beam 210 at a focal point.

In accordance with a particular embodiment of the integrated surgicalsystem, an intermediate focal point 722 is set to fall within, and isscannable in, the conjugate surgical volume 721, which is an imageconjugate of the surgical volume 720, determined by the focusingobjective 700. The surgical volume 720 is the spatial extent of theregion of interest within the eye where imaging and surgery isperformed. For glaucoma surgery, the surgical volume 720 is the vicinityof the irido-corneal angle 13 of the eye.

A pair of transverse scanning mirrors 530, 532 rotated by a galvanometerscanner scan the laser beam 201 in two essentially orthogonaltransversal directions, e.g., in the x and y directions. Then the laserbeam 201 is directed towards a dichroic or polarization beam splitter540 where it is reflected toward a beam combining mirror 601 configuredto combine the laser beam 201 with an OCT beam 301.

Regarding delivery of an OCT beam, an OCT beam 301 output by the OCTimaging apparatus 300 passes through a beam conditioner 511, an axiallymoveable focusing lens 521 and a transversal scanner with scanningmirrors 531 and 533. The focusing lens 521 is used set the focalposition of the OCT beam in the conjugate surgical volume 721 and thereal surgical volume 720. The focusing lens 521 is not scanned forobtaining an OCT axial scan. Axial spatial information of the OCT imageis obtained by Fourier transforming the spectrum of theinterferometrically recombined OCT return beam 301 and reference beams302. However, the focusing lens 521 can be used to re-adjust the focuswhen the surgical volume 720 is divided into several axial segments.This way the optimal imaging spatial resolution of the OCT image can beextended beyond the Rayleigh range of the OCT signal beam, at theexpense of time spent on scanning at multiple ranges.

Proceeding in the distal direction toward the eye 1, after the scanningmirrors 531 and 533, the OCT beam 301 is combined with the laser beam201 by the beam combiner mirror 601. The OCT beam 301 and laser beam 201components of the combined laser/OCT beam 550 are multiplexed and travelin the same direction to be focused at an intermediate focal point 722within the conjugate surgical volume 721. After having been focused inthe conjugate surgical volume 721, the combined laser/OCT beam 550propagates to a second beam combining mirror 602 where it is combinedwith a visual observation beam 401 to form a combined laser/OCT/visualbeam 701.

The combined laser/OCT/visual beam 701 traveling in the distal directionthen passes through the focusing objective 700, and a window 801 of apatient interface, where the intermediate focal point 722 of the laserbeam within the conjugate surgical volume 721 is re-imaged into a focalpoint in the surgical volume 720. The focusing objective 700 re-imagesthe intermediate focal point 722, through the window 801 of a patientinterface, into the ocular tissue within the surgical volume 720.

A scattered OCT return beam 301 from the ocular tissue travels in theproximal direction to return to the OCT imaging apparatus 300 along thesame paths just described, in reverse order. The reference beam 302 ofthe OCT imaging apparatus 300, passes through a reference delay opticalpath and return to the OCT imaging apparatus from a moveable mirror 330.The reference beam 302 is combined interferometrically with the OCTreturn beam 301 on its return within the OCT imaging apparatus 300. Theamount of delay in the reference delay optical path is adjustable bymoving the moveable mirror 330 to equalize the optical paths of the OCTreturn beam 301 and the reference beam 302. For best axial OCTresolution, the OCT return beam 301 and the reference beam 302 are alsodispersion compensated to equalize the group velocity dispersion withinthe two arms of the OCT interferometer.

When the combined laser/OCT/visual beam 701 is delivered through thecornea 3 and the anterior chamber 7, the combined beam passes throughposterior and anterior surface of the cornea at a steep angle, far fromnormal incidence. These surfaces in the path of the combinedlaser/OCT/visual beam 701 create excessive astigmatism and comaaberrations that need to be compensated for.

With reference to FIGS. 9a and 9b , in an embodiment of the integratedsurgical system 1000, optical components of the focusing objective 700and patient interface 800 are configured to minimize spatial andchromatic aberrations and spatial and chromatic distortions. FIG. 9ashows a configuration when both the eye 1, the patient interface 800 andthe focusing objective 700 all coupled together. FIG. 9b shows aconfiguration when both the eye 1, the patient interface 800 and thefocusing objective 700 all detached from one another.

The patient interface 800 optically and physically couples the eye 1 tothe focusing objective 700, which in turn optically couples with otheroptic components of the integrated surgical system 1000. The patientinterface 800 serves multiple functions. It immobilizes the eye relativeto components of the integrated surgical system; creates a sterilebarrier between the components and the patient; and provides opticalaccess between the eye and the instrument. The patient interface 800 isa sterile, single use disposable device and it is coupled detachably tothe eye 1 and to the focusing objective 700 of the integrated surgicalsystem 1000.

The patient interface 800 includes a window 801 having an eye-facing,concave surface 812 and an objective-facing, convex surface 813 oppositethe concave surface. The window 801 thus has a meniscus form. Withreference to FIG. 9c , the concave surface 812 is characterized by aradius of curvature r_(e), while the convex surface 813 is characterizedby a radius of curvature r_(w). The concave surface 812 is configured tocouple to the eye, either through a direct contact or through indexmatching material, liquid or gel, placed in between the concave surface812 and the eye 1. The window 801 may be formed of glass and has arefractive index n_(w). In one embodiment, the window 801 is formed offused silica and has a refractive index n_(w) of 1.45. Fused silica hasthe lowest index from common inexpensive glasses. Fluoropolymers such asthe Teflon AF are another class of low index materials that haverefractive indices lower than fused silica, but their optical quality isinferior to glasses and they are relatively expensive for high volumeproduction. In another embodiment the window 801 is formed of the commonglass BK7 and has a refractive index n_(w) of 1.50. A radiationresistant version of this glass, BK7G18 from Schott AG, Mainz, Germany,allows gamma sterilization of the patient interface 800 without thegamma radiation altering the optical properties of the window 801.

Returning to FIGS. 9a and 9b , the window 801 is surrounded by a wall803 of the patient interface 800 and an immobilization device, such as asuction ring 804. When the suction ring 804 is in contact with the eye1, an annular cavity 805 is formed between the suction ring and the eye.When vacuum applied to the suction ring 804 and the cavity via a vacuumtube a vacuum pump (not shown in FIGS. 9a and 9b ), vacuum forcesbetween the eye and the suction ring attach the eye to the patientinterface 800 during surgery. Removing the vacuum releases or detach theeye 1.

The end of the patient interface 800 opposite the eye 1 includes anattachment interface 806 configured to attach to the housing 702 of thefocusing objective 700 to thereby affix the position of the eye relativeto the other components of the integrated surgical system 1000. Theattachment interface 806 can work with mechanical, vacuum, magnetic orother principles and it is also detachable from the integrated surgicalsystem.

The focusing objective 700 includes an aspheric exit lens 710 having aneye-facing, concave surface 711 and a convex surface 712 opposite theconcave surface. The exit lens 710 thus has a meniscus form. While theexit lens 710 shown in FIGS. 9a and 9b is an aspheric lens giving moredesign freedom, in other configurations the exit lens may be a sphericallens. Alternatively, constructing the exit lens 710 as a compound lens,as opposed to a singlet, allows more design freedom to optimize theoptics while preserving the main characteristics of the optical systemas presented here. With reference to FIG. 9c , the concave surface 711is characterized by a radius of curvature r_(y), while the convexsurface 712 is characterized by an aspheric shape. The aspheric convexsurface 712 in combination with the spherical concave surface 711 resultin an exit lens 710 having varying thickness, with the outer perimeteredges 715 of the lens being thinner than the central, apex region 717 ofthe lens. The concave surface 711 is configured to couple to the convexsurface 813 of the window 801. In one embodiment, the exit lens 710 isformed of fused silica and has a refractive index n_(x) of 1.45.

FIGS. 10a and 10b are schematic illustrations of components of theintegrated surgical system of FIGS. 7 and 8 functionally arranged toform an optical system 1010 having a first optical subsystem 1001 and asecond optical subsystem 1002 that enable access to a surgical volume720 in the irido-corneal angle. Each of FIGS. 10a and 10b includecomponents of the focusing objective 700 and the patient interface 800of FIG. 9a . However, for simplicity, the entirety of the focusingobjective and the patient interface are not included in FIGS. 10a and10b . Also, for additional simplicity in FIG. 10a , the planarbeam-folding mirror 740 of FIGS. 9a and 9b is not included and thecombined laser/OCT/visual beam 701 shown in FIG. 9a is unfolded orstraightened out. It is understood by those skilled in the art thatadding or removing planar beam folding mirrors does not alter theprincipal working of the optical system formed by the first opticalsubsystem and the second optical subsystem. FIG. 10c is a schematicillustration of a beam passing through the first optical subsystem ofFIGS. 10a and 10 b.

With reference to FIG. 10a , a first optical subsystem 1001 of theintegrated surgical system 1000 includes the exit lens 710 of a focusingobjective 700 and the window 801 of a patient interface 800. The exitlens 710 and the window 801 are arranged relative to each other todefine a first optical axis 705. The first optical subsystem 1001 isconfigured to receive a beam, e.g., a combined laser/OCT/visual beam701, incident at the convex surface 712 of the exit lens 710 along asecond optical axis 706, and to direct the beam toward a surgical volume720 in the irido-corneal angle 13 of the eye.

During a surgical procedure, the first optical subsystem 1001 may beassembled by interfacing the convex surface 813 of the window 801 withthe concave surface 711 of the exit lens 710. To this end, a focusingobjective 700 is docked together with a patient interface 800. As aresult, the concave surface 711 of the exit lens 710 is coupled to theconvex surface 813 of the window 801. The coupling may be by directcontact or through a layer of index matching fluid. For example, whendocking the patient interface 800 to focusing objective 700, a drop ofindex matching fluid can be applied between the contacting surfaces toeliminate any air gap that may be between the two surfaces 711, 813 tothereby help pass the combined laser/OCT/visual beam 701 through the gapwith minimal Fresnel reflection and distortion.

In order to direct the beam toward the surgical volume 720 in theirido-corneal angle 13 of the eye, the first optical subsystem 1001 isdesigned to account for refraction of the beam 701 as it passes throughthe exit lens 710, the window 801 and the cornea 3. To this end, andwith reference to FIG. 10c , the refractive index n_(x) of the exit lens710 and the refractive index n_(w) of the window 801 are selected inview of the refractive index n_(c) of the cornea 3 to cause appropriatebeam bending through the first optical subsystem 1001 so that when thebeam 701 exits the subsystem and passes through the cornea 3, the beampath is generally aligned to fall within the irido-corneal angle 13.

Continuing with reference to FIG. 10c and beginning with the interfacebetween the window 801 and the cornea 3. Too steep of an angle ofincidence at the interface where the combined laser/OCT/visual beam 701exits the window 801 and enters the cornea 3, i.e., at the interfacebetween the concave surface 812 of the window and the convex surface ofthe cornea 3, can create excessive refraction and distortion. Tominimize refraction and distortion at this interface, in one embodimentof the first optical subsystem 1001, the refractive index of the window801 is closely matched to the index of the cornea 3. For example, asdescribe above with reference to FIGS. 9a and 9b , the window 801 mayhave a refractive index lower than 1.42 to closely match the cornea 3,which has a refractive index of 1.36.

Excessive refraction and distortion at the interface where the combinedlaser/OCT/visual beam 701 exits the window 801 and enters the cornea 3may be further compensated for by controlling the bending of the beam701 as it passed through the exit lens 710 and the window 801. To thisend, in one embodiment of the first optical subsystem 1001 the index ofrefraction n_(w) of the window 801 is larger than each of the index ofrefraction n_(x) of the exit lens 710 and the index of refraction n_(c)of the cornea 3. As a result, at the interface where the combinedlaser/OCT/visual beam 701 exits the exit lens 710 and enters the window801, i.e., interface between the concave surface 711 of the exit lensand the convex surface 813 of the window, the beam passes through arefractive index change from high to low that cause the beam to bend ina first direction. Then, at the interface where the combinedlaser/OCT/visual beam 701 exits the window 801 and enters the cornea 3,i.e., interface between the concave surface 812 of the exit lens and theconvex surface of the cornea, the beam passes through a refractive indexchange from low to high that cause the beam to bend in a seconddirection opposite the first direction.

The shape of the window 801 is chosen to be a meniscus lens. As such,the incidence angle of light has similar values on both surfaces 812,813 of the window 801. The overall effect is that at the convex surface813 the light bends away from the surface normal and at the concavesurface 812 the light bends towards the surface normal. The effect islike when light passes through a plan parallel plate. Refraction on onesurface of the plate is compensated by refraction on the other surface alight passing through the plate does not change its direction.Refraction at the entering, convex surface 712 of the exit lens 710distal to the eye is minimized by setting the curvature of the enteringsurface such that angle of incidence β of light 701 at the enteringsurface is close to a surface normal 707 to the entering surface at theintersection point 708.

Here, the exit lens 710, the window 801, and the eye 1 are arranged asan axially symmetric system with a first optical axis 705. In practice,axial symmetry is an approximation because of manufacturing andalignment inaccuracies of the optical components, the natural deviationfrom symmetry of the eye and the inaccuracy of the alignment of the eyerelative to the window 801 and the exit lens 710 in a clinical setting.But, for design and practical purposes the eye 1, the window 801, andthe exit lens 710 are considered as an axially symmetric first opticalsubsystem 1001.

With continued reference to FIG. 10a , a second optical subsystem 1002is optically coupled to the first optical subsystem 1001 at an angle αrelative to the first optical axis 705 of the first optical subsystem1001. The advantage of this arrangement is that the both opticalsubsystems 1001, 1002 can be designed at a much lower numerical aperturecompared to a system where all optical components are designed on axiswith a common optical axis.

The second optical subsystem 1002 includes a relay lens 750 that, aspreviously described with reference to FIG. 8, generates a conjugatesurgical volume 721 of the surgical volume 720 within the eye. Thesecond optical subsystem 1002 includes various other componentscollectively indicated as an optical subsystem block 1003. Referring toFIG. 8, these components may include a femtosecond laser source 200, anOCT imaging apparatus 300, a visual observation device 400, beamconditioners and scanners 500, and beam combiners 600.

The second optical subsystem 1002 may include mechanical parts (notshown) configured to rotate the entire subsystem around the firstoptical axis 705 of the first optical subsystem 1001. This allowsoptical access to the whole 360-degree circumference of theirido-corneal angle 13 of the eye 1.

With reference to FIG. 10b , flexibility in arranging the first andsecond optical subsystems 1001, 1002, relative to each other may beprovided by an optical assembly 1004 interposed between the opticaloutput of the second optical subsystem 1002 and the optical input of thefirst optical subsystem 1001. In one embodiment, the optical assembly1004 may include one or more planar beam-folding mirrors 740, prisms(not shown) or optical gratings (not shown) configured to receive theoptical output, e.g., combined laser/OCT/visual beam 701, of the secondoptical subsystem 1002, change or adjust the direction of the combinedlaser/OCT/visual beam, and direct the beam to the optical input of thefirst optical subsystem 1001 while preserving the angle α between thefirst optical axis 705 and the second optical axis 706.

In another configuration, the optical assembly 1004 of planarbeam-folding mirrors 740 further includes mechanical parts (not shown)configured to rotate the assembly around the first optical axis 705 ofthe first optical subsystem 1001 while keeping the second opticalsubsystem 1002 stationary. Accordingly, the second optical axis 706 ofthe second optical subsystem 1002 can be rotated around the firstoptical axis 705 of the first optical subsystem 1001. This allowsoptical access to the whole 360-degree circumference of theirido-corneal angle 13 of the eye 1.

With considerations described above with reference to FIGS. 9a, 9b and9c , the design of the first optical subsystem 1001 is optimized forangled optical access at an angle α relative to the first optical axis705 of the first optical subsystem 1001. Optical access at the angle αcompensates for optical aberrations of the first optical subsystem 1001.Table 1 shows the result of the optimization at access angle α=72degrees with Zemax optical design software package. This design is apractical embodiment for image guided femtosecond glaucoma surgery.

TABLE 1 Center Structure and Refractive Radius Thickness SurfaceMaterial index [mm] [mm] concave Exit lens 710 1.45 −10 4.5 surface offocusing 711, objective. convex Fused silica surface 712 concave Window801 1.50 −10.9 1.0 surface of patient 812, interface. convex BK7G18surface 813 3 Cornea 1.36 −7.83  0.54 8 Aqueous humor 1.32 −6.53 3.5Target Ophthalmic tissue 1.38 N/A 0 to 1 mm

This design produces diffraction limited focusing of 1030 nm wavelengthlaser beams and 850 nm wavelength OCT beams with numerical aperture (NA)up to 0.2. In one design, the optical aberrations of the first opticalsubsystem are compensated to a degree that the Strehl ratio of the firstoptical subsystem for a beam with numerical aperture larger than 0.15 atthe irido-corneal angle is larger than 0.9. In another design, theoptical aberrations of the first optical subsystem are partiallycompensated, the remaining uncompensated aberrations of the firstoptical system are compensated by the second optical subsystem to adegree that the Strehl ratio of the combined first and second opticalsubsystem for a beam with numerical aperture larger than 0.15 at theirido-corneal angle is larger than 0.9.

Calibration

The femtosecond laser source 200, OCT imaging apparatus 300, and visualobservation device 400 of the integrated surgical system 1000 are firstindividually calibrated to ensure their internal integrity and thencross-calibrated for system integrity. The essential part of systemcalibration is to ensure that the when the surgical focus of a laserbeam 201 is commanded to a location of a surgical volume 720, asidentified by the OCT imaging apparatus and/or the visual observationdevice 400, the achieved location of the focus matches the commandedlocation of the focus within a certain tolerance, typically within 5 to10 μm. Also, graphical and cursor outputs, images, overlays displayed ona user interface 110, such as a computer monitor, and user inputs ofocular tissue surgical volume 720 locations accepted from the userinterface 110 should correspond to actual locations in tissue withinpredetermined tolerances of similar accuracy.

One embodiment of this spatial calibration procedure starts with imagingcalibrated scales and scaling magnifications of the OCT imagingapparatus 300 and/or the visual observation device 400 and theirdisplays in a way that the scale value on the display matches the realscale of the calibration target. Then laser calibration patters areexposed or burned into transparent calibration targets, and thecalibration patterns are subsequently imaged. Then, the intendedpatterns and the actual burned patterns are compared with the imagingsystem of the integrated surgical system 1000 or by a separatemicroscope. If they do not match within the specified tolerance, thescaling parameters of the surgical patterns are re-scaled by adjustingthe scaling of the laser beam scanners. This procedure is iterated, ifnecessary, until all spatial calibrations are within tolerance.

Laser Surgery with Ocular Tissue Modification

The anatomy of the eye relevant to the surgical treatment enabled by theintegrated surgical system 1000 disclosed herein is illustrated in FIGS.1-4. To reduce the IOP, laser treatment targets ocular tissues thataffect the trabecular outflow pathway 40. These ocular tissues mayinclude the trabecular meshwork 12, the scleral spur 14, the uveal 15,the corneoscleral meshwork 16, the juxtacanalicular tissue 17, theSchlemm's canal 18, the collector channels 19 within the irido-cornealangle 13.

Disclosed herein is a laser pattern particularly effective in affectingthe trabecular outflow pathway 40. Since the laser interaction volume issmall, on the order of a few micrometers (μm), the interaction of oculartissue with each laser shot of a repetitive laser breaks down oculartissue locally at the focus of the laser. Pulse duration of the laserfor photo-disruptive interaction in ocular tissue can range from severalfemtoseconds to several nanoseconds and pulse energies from severalnanojoules to tens of microjoules. The laser pulses at the focus,through multiphoton processes, breaks down chemical bonds in themolecules, locally photo-dissociate tissue material and create gasbubbles in wet tissue. The breakdown of tissue material and mechanicalstress from bubble formation fragments the tissue and create cleancontinuous cuts when the laser pulses are laid down in proximity to oneanother along geometrical lines and surfaces.

For the sake of the following description the basic interaction volumesare referred to as cells. The size of a cell is determined by the extentof the influence of the laser-tissue interaction. When the laser spots,or cells, are spaced close along a line, the laser creates a narrow,microscopic channel. A wider channel can be created by closely spacing amultitude of laser spots within the cross section of the channel. Forexample, a cylindrical channel can be created by first calculating thecoordinates of the overall position and size of the cylinder. Then,using the size of the cells as a parameter, calculate the coordinates ofeach cell in a closely packed cell arrangement within the volume of thecylinder. The arrangement of the cells resembles the arrangement ofatoms in a crystal structure.

The easiest is to calculate a cubic cell structure, in this case theindividual cells are arranged in regularly spaced rows, columns andsheets, and the coordinates of the cells can be calculated sequentiallyfrom neighbor to neighbor in the order of rows columns and sheets. Thelaser scanner hardware can also follow this regular sequence to scan thelaser beam without excessive jumps. Channels can be created withdifferent cross sections, with oval, rectangular, square or otherregular or irregular cross sections. A channel cut in the ocular tissuecan conduct aqueous humor 8, its conductivity increasing with thecross-sectional area of the channel.

FIGS. 11a and 11b illustrate sectional views of the irido-corneal anglewhere the surgical laser scans to affect a surgical volume 900 (FIG. 11a) to form a channel opening 920 (FIG. 11b ). The surgical volume 900 inthe trabecular meshwork, extends from the anterior chamber 7 and throughthe inner wall of the Schlemm's canal 18. Laser scanning modifies theocular tissue in the surgical volume 900 to create a channel opening920. The channel opening 920 reduces the flow resistance in the oculartissue to increase aqueous flow from the anterior chamber 7 into theSchlemm's canal 18 and thereby reduce the IOP of the eye. The size ofthe channel opening 920 will determine the reduction of the outflow pathresistance and the longevity of effectiveness.

Image guidance is essential for this procedure to locate the structuresprecisely and to monitor the success of the treatment. Minimizing thesize and volume of the treated ocular tissue also helps minimize theamount of gas created and gas-induced tissue movements. As the tissueexpands with the expanding gas, sudden tissue movements can occur whengas escapes from a closed volume and the gas filled void collapses. Suchsudden tissue movements can create discontinuities in the surgicalincisions and should be avoided or minimized.

Another consideration for creating surgical patterns in the oculartissue is the potential shadow effect of the gas bubbles as the incisionprogresses. In general, the incision progresses should proceed from alocation further from the laser and progress towards a location closerto the laser to minimize the shadow effect. The amount of gas is alsoless when the laser is focused tightly to a diffraction limited focalspot and the threshold pulse energy for photo-disruption interaction islowered. When the laser is operated at low threshold, the size of localinteraction volume and the size of the gas bubbles are smaller. Thismeans that the cells filling the surgical volume should be spacedcloser.

Table 2 displays surgical laser and treatment pattern parameters forseveral incisions of different sizes. The range of the parameter set islimited by the Maximum Permissible Exposure (MPE) limit of laser lightentering the eye and practical ranges for the repetition rate of thelaser and the scanning speed of the scanners.

TABLE 2 Channel size Channel Cell size Laser Laser Laser x[mm], crossx[μm], average repetition pulse Procedure Tissue y[mm], section y[μm],power rate energy time treated z[mm] [mm²] z[μm] [W] [kHz] [μJ] [s]Trabecular 1.5, 0.2, 0.2 0.3 3, 3, 3 0.9 300 3 7.4 meshwork Trabecular2, 0.2, 0.2 0.4 4, 4, 4 1 200 5 6.3 meshwork

With respect to MPE, the angled beam path 30 of FIG. 6 is the mostadvantageous since light beams from the femtosecond laser source 200 orthe OCT imaging apparatus 300 transmitted through the tissue do notreach directly the retina. This is in contrast with known corneal andcataract surgeries, where direct laser light or OCT light transmittedthrough the tissue reaches the retina. Therefore, the angled beam path30 of FIG. 6 can use higher beam average power. Higher average power forthe surgical laser results in faster procedure time. Higher averagepower for the OCT beam results in faster OCT image acquisition time forthe same image quality or better image quality for the same imageacquisition time. With respect to cell size and laser pulse energy,smaller cell sizes and pulse energies are preferred to minimize theamount of gas created in the tissue.

Linear perfusion models, experimental (Liu et al., 2005) and clinicalfindings from ELT procedures indicate channel cross sections from 0.24mm² to 0.4 mm² can achieve sufficient IOP reduction. As seen from Table2, the surgical laser procedure enabled by the integrated surgicalsystem disclosed herein can produce similar channel cross sections tothose in Liu et al. and can be completed in less than 10 seconds.

FIG. 12 is a flowchart of a method of reducing intraocular pressure inan eye having a cornea, an anterior chamber, and an irido-corneal anglecomprising an aqueous humor outflow pathway formed of a trabecularmeshwork, a Schlemm's canal, and one or more collector channelsbranching from the Schlemm's canal, the method comprising. The methodmay be performed by the integrated surgical system 1000 of FIGS. 7-10 b.

At step 1202, an OCT beam 301 is delivered through the cornea 3 and theanterior chamber 7 into the irido-corneal angle 13. In one embodiment,the OCT beam 301 has a resolution less than or equal to approximately 5micrometers and is delivered to the irido-corneal angle 13 by directingthe OCT beam to a first optical subsystem 1001 that includes a window801 coupled to the cornea 3 and an exit lens 710 coupled to the window.

At step 1204, an OCT image of a portion of the irido-corneal angle 13 isacquired based on the OCT beam 301 delivered to the irido-corneal anglethrough the first optical subsystem 1001. To this end, an OCT returnbeam 301 is received through the first optical subsystem 1001 andprocessed at an OCT imaging apparatus 300 using known OCT imagingtechniques.

At step 1206, a surgical volume 900 of ocular tissue to be modified isdetermined based on the OCT image. The surgical volume 900 may bedetermined based on a 2D cross-sectional OCT image that is displayed ona control system 100 of the integrated surgical system 1000. A visualobservation beam 401 may also be used to determine the surgical volume900. To this end, a visual observation beam 401 may be acquired from theirido-corneal angle 13 by a microscope 400 through the first opticalsubsystem 1001, and the volume 900 of ocular tissue to modify may bedetermined by presenting the OCT image and visual observation signaloverlaid on a display screen of the control system 100. Alternatively,the OCT image and visual observation signal may be registered on adisplay screen.

In one embodiment, the Schlemm's canal 18 is characterized by acircumference, and the surgical volume 900 of ocular tissue to modify isdetermined based on the density of collector channels 19 around thecircumference. In this case, a density distribution of collectorchannels 19 around at least a portion of the circumference of theSchlemm's canal 18 is determined based on OCT images. A region of theSchlemm's canal 18 having a density above a threshold criterion isidentified, and the proximity of the identified region is included inthe volume of ocular tissue to modify. The criterion may be the 50^(th)percentile of the distribution, the 75^(th) percentile, or a numericalvalue higher than the 75^(th) percentile. In another embodiment, thevolume 900 of ocular tissue to be modified is in the proximity of one ormore of the collector channels 19.

At step 1208, each of an OCT beam 301 and a laser beam 201 is deliveredthrough the cornea 3, and the anterior chamber 7 into the irido-cornealangle 13. In one embodiment, the OCT beam 301 and laser beam 201 havesubstantially equal resolutions, e.g., less than or equal toapproximately 5 micrometers, and each beam is delivered to theirido-corneal angle by directing each beam to a first optical subsystem1001 that includes a window 801 coupled to the cornea 3 and an exit lens710 coupled to the window. The OCT beam 301 and the laser beam 201 maybe collinearly directed to the first optical subsystem 1001 along a sameoptical path, for example by multiplexing the beams. Alternatively, theOCT beam 301 and the laser beam 201 may be non-collinearly directed tothe first optical subsystem at the same time along spatially separatedor angled optical paths.

Distortion and aberrations of the beams 201, 301 caused by oblique angleentry into the eye are compensated for by directing each beam into thefirst optical subsystem 1001 at an angle. To this end, the eye 1includes a direction of view and the first optical subsystem 1001 ispositioned relative to the eye so as to include a first optical axis 705that is substantially aligned with the direction of view of the eye. Thebeams 201, 301 are input to the first optical subsystem 1001 bydirecting each beam into a convex surface 713 of the exit lens 710 alonga second optical axis 706 offset from the first optical axis 705 by anangle α. Additionally, each beam 201, 301 may be directed into theconvex surface 713 of the exit lens 710 at an angle β relative to asurface normal 707 to the convex surface.

At step 1210, a volume 900 of ocular tissue within the trabecularoutflow pathway 40 is modified to reduce a pathway resistance present inone or more of the trabecular meshwork 12, the Schlemm's canal 18, andthe one or more collector channels 19 by applying the laser beam 201 toocular tissue defining the volume. To this end, a laser beam 201 havinga wavelength between 330 nanometers and 2000 nanometers may be scannedin multiple directions to interact with the ocular tissue defining thesurgical volume 900. The laser beam 201 may be applied in a continuousmanner or as a multitude of laser pulses with a pulse duration between20 femtoseconds and 1 nanosecond. The laser beam 201 causesphoto-disruptive interaction with the ocular tissue to reduce thepathway resistance or create a new outflow pathway 40. In oneembodiment, photo-disruptive interaction with the ocular tissue createsa channel 902 opened through the trabecular meshwork connecting theanterior chamber and the Schlemm's canal.

Accessing the Irido-Corneal Angle

FIG. 13 is a flowchart of a method of directing a light beam to anirido-corneal angle of an eye having a direction of view and a corneawith a refractive index n_(c). The method may be performed by theintegrated surgical system 1000 of FIGS. 7-10 b.

At step 1302, a first optical subsystem 1001 and a second opticalsubsystem 1002 are arranged relative to each other. The first opticalsubsystem 1001 includes a window 801 formed of a material with arefractive index n_(w). The window 801 has a concave surface 812 and aconvex surface 813 opposite the concave surface. The first opticalsubsystem 1001 also includes and an exit lens 710 formed of a materialhaving a refractive index n_(x). The exit lens 710 has a concave surface711 and a convex surface 712 opposite the concave surface. The concavesurface 711 of the exit lens 710 is configured to couple to the convexsurface 813 of the window 801 to define a first optical axis 705extending through the window and the exit lens. The concave surface 812of the window 801 is configured to detachably couple to the cornea 3 ofthe eye such that the first optical axis 705 is generally aligned withthe direction of view of the eye.

At step 1304, a light beam output by the second optical subsystem 1002is directed to be incident at the convex surface 712 of the exit lens710 along a second optical axis 706 at an angle α that is offset fromthe first optical axis 705. To this end, the second optical subsystem1002 or another intermediate optical assembly 1004 may be configured todetermine a measure of angle separation between the first optical axisand the second optical axis, and to adjust the orientation of the secondoptical axis until the angle of separation is at angle α. The angle α istypically greater than 30 degrees. More specifically, the angle α may bebetween 60 degrees and 80 degrees. Even more specifically, the angle αis approximately 72 degrees.

At step 1306, the light beam output by the second optical subsystem 1002may be also directed to intersect the convex surface 712 of the exitlens 710 at an intersection point and an angle β between the secondoptical axis 706 and a surface normal 707 to the convex surface of theexit lens. Again, the second optical subsystem 1002 or anotherintermediate optical assembly 1004 may be configured to determine ameasure of angle separation between the second optical axis and thesurface normal 707, and to adjust the orientation of the second opticalaxis until the angle of separation is at angle β.

In some arrangements, as shown for example in FIG. 10b , the secondoptical subsystem 1002 may be configured to be arrange relative to thefirst optical subsystem 1001 so that the light beam 701 is output by thesecond optical subsystem along an axis offset from the second opticalaxis 706. In these cases, in the directing process of block 1304, thelight beam 701 is received at an optical assembly 1004 interposedbetween the first optical subsystem 1001 and the second opticalsubsystem 1002 and redirected into general alignment with the secondoptical axis 706. The second optical axis 706 may be rotated around thefirst optical axis 705 while maintaining the second optical axis offsetfrom the first optical axis by an angle substantially equal to the angleα. Doing so allows for treatment around the circumference of theirido-corneal angle 13. In configurations where the second optical axis706 intersects the convex surface 712 of the exit lens 710 at anintersection point 708 and at an angle β between the second optical axisand a surface normal 707 to the convex surface of the exit lens, thedirecting process of block 1306 involves rotating the second opticalaxis around the first optical axis while also maintaining an anglebetween the second optical axis and the surface normal that issubstantially equal to the angle β.

The various aspects of this disclosure are provided to enable one ofordinary skill in the art to practice the present invention. Variousmodifications to exemplary embodiments presented throughout thisdisclosure will be readily apparent to those skilled in the art. Thus,the claims are not intended to be limited to the various aspects of thisdisclosure, but are to be accorded the full scope consistent with thelanguage of the claims. All structural and functional equivalents to thevarious components of the exemplary embodiments described throughoutthis disclosure that are known or later come to be known to those ofordinary skill in the art are expressly incorporated herein by referenceand are intended to be encompassed by the claims. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the claims. No claimelement is to be construed under the provisions of 35 U.S.C. § 112,sixth paragraph, unless the element is expressly recited using thephrase “means for” or, in the case of a method claim, the element isrecited using the phrase “step for.”

It is to be understood that the embodiments of the invention hereindescribed are merely illustrative of the application of the principlesof the invention. Reference herein to details of the illustratedembodiments is not intended to limit the scope of the claims, whichthemselves recite those features regarded as essential to the invention.

What is claimed is:
 1. A method of reducing intraocular pressure in aneye having a cornea, an anterior chamber, and an irido-corneal anglecomprising an aqueous humor outflow pathway formed of a trabecularmeshwork, a Schlemm's canal, and one or more collector channelsbranching from the Schlemm's canal, the method comprising: deliveringeach of an optical coherence tomography (OCT) beam and a laser beamthrough the cornea, and the anterior chamber into the irido-cornealangle; and modifying a volume of ocular tissue within the outflowpathway to reduce a pathway resistance present in one or more of thetrabecular meshwork, the Schlemm's canal, and the one or more collectorchannels by applying the laser beam to ocular tissue defining the volumeto thereby cause photo-disruptive interaction with the ocular tissue toreduce the pathway resistance or create a new outflow pathway.
 2. Themethod of claim 1, wherein delivering each of an OCT beam and a laserbeam comprises directing each beam to a first optical subsystemcomprising a window coupled to the cornea and an exit lens coupled tothe window.
 3. The method of claim 2, wherein: the eye comprises adirection of view and the first optical subsystem comprises a firstoptical axis substantially aligned with the direction of view, anddirecting each beam to the first optical subsystem comprises directingeach beam into the first optical subsystem along a second optical axisoffset from the first optical axis by an angle α.
 4. The method of claim3, wherein the exit lens comprises a convex surface and directing eachbeam to the first optical subsystem further comprises directing eachbeam into the convex surface of the exit lens at an angle β relative toa surface normal to the convex surface.
 5. The method of claim 1,wherein the OCT beam and the laser beam are collinearly directed.
 6. Themethod of claim 1, wherein the OCT beam and the laser beam arenon-collinearly directed.
 7. The method of claim 1, wherein applying thelaser beam comprises scanning the laser beam to interact with the oculartissue defining the volume.
 8. The method of claim 1, whereinphoto-disruptive interaction with the ocular tissue creates a channelopened through the trabecular meshwork connecting the anterior chamberand the Schlemm's canal.
 9. The method of claim 1, wherein thewavelength of the laser beam is between 330 nanometers and 2000nanometers.
 10. The method of claim 1, wherein the laser beam iscomposed of a multitude of laser pulses with pulse duration between 20femtoseconds and 1 nanosecond.
 11. The method of claim 1, wherein thevolume of ocular tissue is in a proximity of one or more of thecollector channels.
 12. The method of claim 1, wherein the laser beamand the OCT beam have respective resolutions that are substantiallyequal.
 13. The method of claim 12, wherein the resolution is less thanor equal to approximately 5 micrometers.
 14. The method of claim 1,further comprising, prior to delivering each of an OCT beam and a laserbeam: delivering an OCT beam through the cornea and the anterior chamberinto the irido-corneal angle; acquiring an OCT image of a portion of theirido-corneal angle; and determining the volume of ocular tissue tomodify based on the OCT image.
 15. The method of claim 14, wherein theOCT image comprises a two-dimensional cross-sectional image.
 16. Themethod of claim 14, wherein determining the volume of ocular tissue tomodify comprises presenting the OCT image on a display screen.
 17. Themethod of claim 14, wherein the Schlemm's canal is characterized by acircumference, and determining the volume of ocular tissue to modifycomprises: determining a density distribution of collector channelsaround at least a portion of the circumference of the Schlemm's canal;identifying a region of the Schlemm's canal having a density above athreshold criterion; and including a proximity of the identified regionin the volume of ocular tissue to modify.
 18. The method of claim 14,further comprising acquiring a visual observation signal from theirido-corneal angle.
 19. The method of claim 18, wherein determining thevolume of ocular tissue to modify comprises presenting the OCT image andvisual observation signal overlaid on a display screen.
 20. The methodof claim 18, wherein determining the volume of ocular tissue to modifycomprises presenting the OCT image and visual observation signalregistered on a display screen.